# Neuroprotective Mechanisms of Hyperbaric Oxygen Therapy in Cerebral Ischemia-Hypoxia Injury Following Cardiopulmonary Resuscitation

## TL;DR

This paper reviews how hyperbaric oxygen therapy may protect the brain after cardiac arrest by reducing injury caused by low oxygen and inflammation.

## Contribution

The paper proposes a novel combined therapeutic strategy integrating hyperbaric oxygen with CPR and adjunctive therapies for post-resuscitation brain injury.

## Key findings

- Hyperbaric oxygen therapy modulates oxidative stress and neuroinflammation after cerebral ischemia.
- HBO upregulates endogenous antioxidants and stabilizes mitochondrial function in hypoxic-ischemic injury.
- The therapy shows potential in addressing global cerebral ischemia following CPR through multiple injury mechanisms.

## Abstract

Despite significant advancements in cardiopulmonary resuscitation (CPR) techniques, the global burden of sudden cardiac death remains high, with post-CPR survival rates persistently below 8%. Hypoxic-ischemic brain injury (HIBI) is the predominant cause of mortality, accounting for 68% of fatalities following resuscitation. Hyperbaric oxygen (HBO) therapy, which enhances oxygen dissolution in plasma, has demonstrated efficacy in focal cerebral ischemia conditions such as stroke. However, its potential in addressing global cerebral ischemia following CPR—a condition pathophysiologically distinct due to the absence of a salvageable ischemic penumbra and characterized by pan-cerebral energy failure—remains insufficiently explored. This review synthesizes emerging evidence from both focal and global ischemia models, highlighting the role of HBO in modulating key injury mechanisms common to both conditions, including oxidative stress, neuroinflammation, and ferroptosis. By integrating findings on HBO-induced upregulation of endogenous antioxidants, suppression of pro-inflammatory cytokines, and stabilization of mitochondrial function, we propose a combined therapeutic strategy that incorporates HBO with advanced CPR techniques and adjunctive therapies to mitigate HIBI.